Malaria

Malaria Life
Cycle
Life Cycle

Sporogony
Oocyst
Sporozoites
Mosquito Salivary
Gland

Zygote

Exoerythrocytic
(hepatic) cycle

Gametocytes

Erythrocytic
Cycle

Schizogony

Hypnozoites
(for P. vivax
and P. ovale)

Plasmodium spp.
1.Plasmodium vivax : Benign Tertian,
Tertian Malaria
2.Plasmodium ovale : Ovale tertian
Malaria
3.Plasmodium malariae : Quartan malaria
4.Plasmodium falciparum : Malignant
Tertian malaria.

Affinity of Parasite to
Erythrocytes
P.vivax
P.malariae
or
P.ovale

Infectes only young

P.falciparum
groups

Infects all age

Old Erythocytes

Alteration of Host Cells

A variety of structural changes, which alter
its function, appearance or antigenicity.
These alterations are a consequence of
parasite growth
Advantage to the parasite (e.g. increased
membrane permeability, increased selective
intake of nutrients, or escape from immunity
by sequestration).
The nature of the alterations induced are
variable from one species to another.

The alterations identified

include
:
1. A visible change of shape
and reduced deformability
2. The presence of electrondense protrusions or
'knobs
3. The presence of small
depressions, or
"caveolae", at the surface
of the red cell, connected
by a network of small
vesicles and clefts in P.
vivax and P. ovale

4.
5.

6.

The alterations identified

include :

The cytoadherence to
endothelial cells
The adherence to normal
erythrocytes ("rosetting") or to
other infected erythrocytes
("auto-agglutination or
clumping)
The presence of new metabolic
channels; evidence of new
parasite-specific antigens
associated with the red cell
membrane

Pathogenesis
Related to erythrocytic infection by the asexual
stages, Gametocytes not involve in
pathogenesis
Pathology is associated with:
Haemolysis
- Direct invasion & rupture of RBC during erythrocytic cycle
- Increased osmotic fragility of RBC

Increased adhesiveness of infected RBC

- Increases with the maturity of the parasite (schizont > trophozoite)
- Knob theory

Release of pyrogens, toxin and cytokines

Immunological responses
Capillary permeability
Tissue hypoxia

Pathogenesis

Rosetting

Sequestration
Sludging

Pathogenesis
Cytoadherence seems to be the main culprit
for
pathogenesis
Infected RBCs will adhere to the endothelium
as
High cytokine levels
well as to each other
induce
expression of endothelial

adhesins -- inflammation
makes the
canendothelia
induce (mimic) many of symptoms
Cytokines
stickier
and
signs of malaria (shivering, headache, chills,

spiking fever,sweating, vasodilation,

hypoglycemia)
Adherence and inflammation reinforce each other
in an unholy circle causing pathology

Immunity
Influenced by
Genetics
Age
Health condition
Pregnancy status
Intensity of transmission in region
Length of exposure
Maintenance of exposure

Immunity
Innate
Red cell polymorphisms associated with
some protection

Hemoglobin S sickle cell trait or disease

Hemoglobin C and hemoglobin E
Thalessemia and
Glucose 6 phosphate dehydrogenase
deficiency (G6PD)

Red cell membrane changes

Absence of certain Duffy coat antigens
improves resistance to P.v.

Immunity
Acquired
Transferred from mother to child
3-6 months protection
Then children have increased susceptibility

Increased susceptibility during early childhood

Hyper- and holoendemic areas
By age 5 attacks usually < frequent and severe
Can have > parasite densities with fewer symptoms

Meso- or hypoendemic areas

Less transmission and repeated attacks
May acquire partial immunity and be at higher risk for
symptomatic disease as adults

Immunity
Acquired
No complete immunity
Can be parasitemic without clinical disease

Need long period of exposure for induction

May need continued exposure for
maintenance
Immunity can be unstable
Can wane as one spends time outside endemic
area
Can change with movement to area with
different endemicity
Decreases during pregnancy, risk improves
with increasing gravidity

Immune Mechanisms
Stage specific :
Anti sporozoite antibodies in adults in
endemic areas- blocks liver invasion
Anti sporozoite/merozoite antibodies block rbc invasion
Cytokines : TNF blocks merozoite
development; IL1 ; IL10
Erythrocyte clearance - liver and spleen
Block cyto-adherence
Enhance clearance through opsonisation
ADCC likely
NK activity

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